Synergistic compositions of immunostimulating reconstituted influenza virosomes with immunopotentiators and vaccines containing them

Abstract

The present invention is directed to a preparation of an adjuvant system to achieve required level of humoral and cellular immune response against antigen of interest. The current invention provides an adjuvant system comprising an immunostimulating reconstituted influenza virosomes (IRIVs) and immunopotentiators. The current invention illustrates that an antigen is adsorbed or incorporated into IRIVs and further formulated with lipophilic adjuvant such as MPL or glucopyranosyl lipid adjuvant (synthetic analogue of MPL).

We claim: 
     
         1 . An immunogenic composition comprising:
 (a) an antigen; and   (b) an adjuvant system   wherein an adjuvant system comprises a delivery system and immunopotentiator(s).   
     
     
         2 . The immunogenic composition as claimed in  claim 1 , wherein delivery system is virosome. 
     
     
         3 . The immunogenic composition as claimed in  claim 2 , wherein virosome is an immunostimulating reconstituted influenza virosomes. 
     
     
         4 . The immunogenic composition as claimed in  claim 3 , wherein immunostimulating reconstituted influenza virosomes comprising mixture of phospholipids, essentially reconstituted functional virus envelopes and biologically active HA or derivative thereof. 
     
     
         5 . The immunogenic composition as claimed in  claim 1 , wherein immunopotentiator(s) is an adjuvant. 
     
     
         6 . The immunogenic composition as claimed in  claim 5 , wherein the adjuvant is selected from alum based adjuvants, mineral salt adjuvants, Complete Freund's adjuvant (CFA), Incomplete Freund's adjuvant (IFA), montanide, MF 59 and Adjuvant 65, bacterially derived adjuvants, lipophilic adjuvants, hydrophillic adjuvants or their suitable combinations. 
     
     
         7 . The immunogenic composition as claimed in  claim 6 , wherein mineral salt adjuvants is selected from salts of calcium, iron and zircon turn or their suitable combinations. 
     
     
         8 . The immunogenic composition as claimed in  claim 6 , wherein lipophilic adjuvant is selected from Telormedix, Mono Phosphoryl Lipid A, glucopyranosyl lipid adjuvant and suitable combinations thereof. 
     
     
         9 . A method for preparation of immunogenic composition comprising:
 (a) Formulation of virosome;   (b) Adsorption or incorporation, of antigen to prepare modified virosome having antigen;   (c) Addition of adjuvant to the modified virosome having adsorbed antigen   
     
     
         10 . The method as claimed in  claim 9 , wherein the virosome is an immunostimulating reconstituted influenza virosomes. 
     
     
         11 . The method as claimed in  claim 9 , wherein adjuvant can be selected from hydrophilic adjuvants and lipophilic adjuvants. 
     
     
         12 . The method as claimed in  claim 11 , wherein hydrophilic adjuvants is covalently linked to the surface of the virosome through cross-linkers. 
     
     
         13 . An adjuvant system comprising:
 (a) delivery system or vehicle; and   (b) immunopotentiator(s)   
     
     
         14 . The adjuvant system as claimed in  claim 13 , wherein delivery system is virosome. 
     
     
         15 . The adjuvant system as claimed in  claim 13 , wherein virosome is an immunostimulating reconstituted influenza virosomes. 
     
     
         16 . The adjuvant system as claimed in  claim 14 , wherein immunopotentiator(s) is an adjuvant selected from Alum based adjuvants, mineral salt adjuvants, Complete Freund's adjuvant (CFA), Incomplete Freund's adjuvant (IFA), montanide, MP 59 and Adjuvant 65, bacterially derived adjuvants, lipophilic adjuvants, hydrophilic adjuvants. 
     
     
         17 . The adjuvant system as claimed in  claim 16 , wherein lipophilic adjuvant is selected from Telormedix, Mono Phosphoryl Lipid A, glucopyranosyl lipid adjuvant and combination thereof. 
     
     
         18 . An adjuvant system as claimed in  claim 13  comprising:
 (a) Virosome; and 
 (b) glucopyranosyl lipid adjuvant 
 
     
     
         19 . The adjuvant system as claimed in  claim 18 , wherein virosome is an immunostimulating reconstituted influenza virosomes. 
     
     
         20 . A method of preparation of adjuvant system as claimed in  claim 13  comprising:
 (a) formulating a modified virosome with lipophilic antigen or hydrophilic antigen 
 (b) Addition of adjuvant into modified virosome having antigen. 
 
     
     
         21 . A pharmaceutical composition comprising immunogenic composition as claimed in  claim 1 , optionally with pharmaceutically acceptable carrier or excipient for inducing an immune response against antigen. 
     
     
         22 . A vaccine containing immunogenic composition as claimed in  claim 1 , for inducing an immune response against antigen. 
     
     
         23 . A method of stimulating immune response of a patient in need thereof comprising administering a suitable dosage of immunogenic composition according to any one of  claims 1  to  22 . 
     
     
         24 . The immunogenic composition as claimed in any preceding claim, wherein antigen is selected from  Leishmania,  HIV, hepatitis C virus (HCV), tuberculosis and herpes simplex virus (HSV), malaria causing parasites, Human papilloma virus, preferably  Leishmania  antigen. 
     
     
         25 . The immunogenic composition as claimed in  claim 24 , wherein  Leishmania  antigen is selected from Leish F3, VID 94, VID 99, VID 105, VID 111, KMP 11, LJL 143, Leish F1 and Leish F2; preferably Leish F3 or KMP 11 or LJL 143.